Battle Brewing over Third-Party Inspections

Originally Published MDDI September 2002

WASHINGTON WRAP-UP

As public trust in corporate leaders wanes, legislators may frown on reforms allowing private-sector alternatives to FDA inspections.

James G. Dickinson

FDA District Director Joins Abbott | Crawford for FDA Commissioner? | Congress Questions FDA on Mentor Probe | Clinical Trial Recruiting Fees Should Be Disclosed | FDA Orders CryoLife Tissue Recall

A classic Washington battle over medical device user fees and third-party inspections was looming over Congress as it adjourned for its August recess. The combatants: proponents of strong government versus those supporting free-market forces.

Adding fuel to the confrontation was voter unrest over corporate malfeasance and its effects on Wall Street. A USA Today poll published in July suggested that the scandals have increased public trust in government intervention. Accordingly, lawmakers are more skittish than usual ahead of the November elections.

Is now the right time to permit some regulation-mandated inspections of medical device facilities to be performed by private auditors chosen and paid by the companies being inspected? And who might such auditors be? The same consultants who advise the companies about their compliance with FDA regulations? Shades of Arthur Andersen!

The Washington Post presented the issue on July 16 under the headline, "Bill Would Curtail FDA Power: Bush Backs Changes on Medical Devices." It quoted a spokesman for Senator Edward Kennedy (D–MA) as saying he was "very concerned about the idea of a regulated industry choosing its inspectors and third-party reviewers. It's an inherent conflict of interest that could lead to a potential tragedy." Kennedy is chairman of the key FDA-monitoring Committee on Health, Education, Labor, and Pensions.

The pending legislation would allow companies to pick from an FDA-vetted list of inspection and device-review firms. The agency would retain authority to oversee both inspections and product reviews conducted by these third parties, and to reject their findings.

However, as has happened on the drug side, unsettling perceptions of ineptness and even impropriety may result. For example, earlier this year, FDA's Center for Drug Evaluation and Research approved Schering-Plough's new drug, Clarinex. At the time, the company was under both regulatory and criminal investigation for good manufacturing practices violations.

As part of the approval, the center accepted a private manufacturing audit of the facility where Clarinex would be made. The audit, by Lachman Consulting, was conducted in lieu of an FDA preapproval inspection at Schering-Plough's request.

Later, Schering-Plough entered into a record $500 million consent decree with FDA over its manufacturing problems. The center has so far failed to release the Lachman audit under the Freedom of Information Act, saying such requests are backlogged for years owing to scarce resources.

Whether statute-authorized private inspections of regulated companies would be as accessible to public scrutiny as FDA's own inspections remains an unanswered question.

The legislation has the support of AdvaMed, but not that of the smaller Medical Device Manufacturers Association, which says smaller companies can't afford user fees. Despite the emerging controversy, AdvaMed said in July that it remains confident that a medical device user-fee bill, including provisions on third-party inspections and reviews, will make it to President Bush's desk during this Congress.

FDA District Director Joins Abbott

Continuing its practice of hiring former senior FDA officials, Abbott Laboratories (Abbott Park, IL) has now named FDA Atlanta District director Ballard Graham to a vice presidency. Previous hires from FDA include former Center for Biologics Evaluation and Research deputy director Michael Beatrice and former Office of Generic Drugs director Douglas Sporn.

A 35-year veteran of the agency, Graham joined Abbott in August as vice president for corporate regulatory affairs. As previously reported here, Abbott is struggling to please FDA with its compliance with a 1999 consent decree on its diagnostics manufacturing operations.

Graham's recruitment is apparently an effort by the company to open stronger communication with FDA. Ballard told John Scharmann, himself a former FDA Denver District director, that part of his responsibilities will be dealing with third- party contracts.

Abbott recently discontinued its association with Quintiles Consulting, while maintaining that it was not disappointed with Quintiles' performance. (Like Abbott, Quintiles is rich in former FDA leaders, including former CDRH compliance director Ron Johnson).

Crawford for FDA Commissioner?

A close associate of influential senator Orrin Hatch (R–UT) says deputy FDA commissioner Lester Crawford is again in the running for the agency's top job. Hatch has a longstanding interest and involvement in FDA affairs and mentored David Kessler's run for commissioner.

Veterinarian Crawford was an early candidate, and had been rumored to be the choice of Health and Human Services secretary Tommy Thompson. Then his candidacy encountered resistance from some consumer lobbyists who cited his prior connections with food industry interests.

Now, however, the Hatch source says Crawford's performance as deputy is getting such good grades that it would not be surprising if he were soon nominated to be the permanent commissioner.

Numerous editorial and industry voices in Washington have begun criticizing the policy drift that the protracted lack of a permanent commissioner has created at this key agency.

Congress Questions FDA on Mentor Probe

The House Commerce Committee wants to know whether a "long-standing and ongoing" FDA criminal investigation of breast implant maker Mentor Corp. (Santa Barbara, CA) is open or resolved. Committee chairman W.J. "Billy" Tauzin (R–LA) and Oversight and Investigations Subcommittee chairman Jim Greenwood (R–PA) asked this question of FDA deputy commissioner Lester Crawford in a July 11 letter.

If the criminal probe is inactive or closed, the committee wants FDA to turn over to it "all records of the criminal investigation of the allegations against Mentor Corporation." The existence of an FDA investigation was confirmed in committee documents obtained by this writer in April of 2000. Those documents indicated that the investigation was "based on allegations of serious irregularities in breast implant studies."

At that time, Mentor denied that such an investigation was ongoing. The company instead said that FDA's probe focused on "manufacturing issues" involved in the making of silicone breast implants. Following the July 11 letter, Mentor did not return a call requesting comment.

The committee's interest in Mentor comes after a presentation by the company at an FDA advisory committee meeting on July 9 that delved into postmarketing data involving saline-filled breast implants that were approved in 2000. FDA panel members criticized the company for a lack of data on reported complications in patients "lost to follow-up." In contrast, the FDA panel praised Mentor's competitor, Inamed (Santa Barbara, CA), for having better data on its silicone breast implants, which were approved at the same time.

Inamed's data showed that two-thirds of women who have undergone breast implant surgery needed additional surgery. The problems corrected ranged from leakage and wrinkling to deflation of the implant and tightening of the scar tissue around the implant.

The July 11 letter pointed out that some advisory committee members had expressed "serious concerns about both the results and the nature of the [mentor] studies [with phrases] such as 'mind-boggling poor results,' 'high rates of product failure,' and 'astoundingly weak.'"

In what may be a hint of a future hearing before the November elections, the letter reminded Crawford that the committee had examined FDA's oversight and regulation of breast implants in the past.

Clinical Trial Recruiting Fees Should Be Disclosed

Medical device companies that conduct clinical trials of their products should be careful when offering money or other inducements to physicians who recruit patients for those trials. That's the advice of James Sheehan, who has prosecuted over 500 fraud cases involving clinical trials. Sheehan is Chief of the Civil Trial Division of the Philadelphia U.S. Attorney's Office.

Sheehan's comments came at a Drug Information Association meeting in Chicago last June. He told attendees that clinical trial subjects should be made aware of the incentives that are being given to doctors to recruit them because "a jury would think" that way.

Sheehan urged trial sponsors to be careful with incentives and alert to the temptations investigators may have to "fudge" inclusion criteria in clinical trials. "Whenever you have a fraud case," he said, "there are people either looking the other way or letting things happen or not looking too closely because of their economic interest."

In strolling through the Chicago conference's exhibit area, Sheehan said, he saw "some very interesting displays." But he stopped short of identifying explicit problems there with patient recruitment techniques.

"There are some very interesting patient recruitment centers," he generalized. "I like the wheels, I like the cruises, I like the cash, I like the faxes saying 'we need so many more patients to recruit for this trial, we will pay the physicians $5000 or $1800 per patient if they bring a study; we'll pay the clinical coordinators $50 for each patient they bring in the study.'"

"What do you tell the patient about the recruitment fee?" Sheehan asked. "How can you not tell the patient about the recruitment fee? If anything happens after the fact to that patient as a result of the study, isn't that something they should have known?"

Sheehan urged sponsors to "take a look" if something by a clinical investigator seems "too good to be true." Recent publicity about research abuse, he warned, has brought "an exponential increase" in the number of whistle-blowers coming forward. In some cases their incentive is a 15% share of the legal recovery awarded by the courts.

He cited a Harvard Medical School proposal made by leading NIH institutions to the National Medical College Association on February 8, 2001. According to that proposal, expectations of clinical research sponsors should include the following:

FDA Orders CryoLife Tissue Recall

In an August 14 talk paper, FDA announced that it has ordered Cryolife Inc. (Kennesaw, GA) to recall distributed human tissues processed on or after October 3, 2001. According to the agency, the company cannot ensure that the human tissue it processes for transplantation is free from fungal and bacterial contaminants. In addition, Cryolife must destroy or withhold marketing of tissue processed after that date. Such tissue has been associated, FDA says, with the death on November 7, 2001, of a patient who received a soft tissue implant during reconstructive knee surgery.

The talk paper quoted FDA deputy commissioner Lester Crawford as saying that the order "not only protects patients from the unacceptable level of risk associated with tissue processed by Cryolife, it sends a clear signal that FDA stands ready to take whatever action is necessary to ensure the safety of human tissue."

An inspection of the Cryolife facility from March 25 through April 12 found numerous regulatory violations, resulting in an FDA warning letter to the firm on June 17. According to the letter, Cryolife had not adequately investigated its validation of processing and testing methods. Neither, the letter added, had the company implemented recommendations from the Centers for Disease Control and Prevention, or any other procedures, to ensure that processed tissue was not contaminated.

According to the talk paper, FDA's present concerns focus on bacterial and fungal contamination of soft tissues, including cartilage and tendons. The agency's investigation revealed, among other things, that Cryolife failed to follow many of its own standard operating procedures to prevent infectious disease contamination or cross-contamination. Moreover, says FDA, Cryolife improperly distributed tissue from a donor after confirming the presence of harmful microorganisms in the donor's other tissue samples.

FDA's Center for Devices and Radiological Health is currently investigating the potential risks posed by Cryolife heart valves. If appropriate, the talk paper states, the center will take further regulatory action.

A company spokesman responded to these developments on August 15. "Cryolife has been cooperating with FDA officials since the initial investigation," he said. "Cryolife has implemented many of the CDC recommendations that were made to us. We have a long history of providing allograft tissues—providing safe allograft tissues—to people that have very few medical surgical options. We have requested a hearing with FDA to discuss the matter with them, and we are looking forward to a prompt and constructive meeting."

Copyright ©2002 Medical Device & Diagnostic Industry